Treatment of gastro-intestinal disorders

ABSTRACT

A method of treating chronic disorders associated with the presence of abnormal microflora or an abnormal distribution of microflora in the gastrointestinal tract involves removing the host&#39;s existing enteric microflora and substitution of feces from a disease screener donor or composition comprising microorganism selected from the group consisting of Bacteroides and  E. coli.

This is a continuation of application Ser. No. 08/103,176, filed Aug. 6,1993, now U.S. Pat. No. 5,443,826, which is a continuation of Ser. No.06/646,784, filed on Jan. 24, 1991.

TECHNICAL FIELD

The present invention relates to methods of treating diseases inmammals, in particular to the treatment of chronic disorders associatedwith the presence of abnormal or an abnormal distribution of microflorain the gastrointestinal tract. The invention also relates topharmaceutical compositions suitable for the treatment of suchdisorders.

BACKGROUND ART

There are large numbers of patients suffering from gastro-intestinalsymptoms referrable to the lower small bowel and large bowel which todate have eluded explanation. These disorders include irritable bowelsyndrome (IBS) or spastic colon, idiopathic ulcerative colitis, mucouscolitis, collagenous colitis, Crohn's disease, inflammatory boweldisease in general, microscopic colitis, antibiotic-associated colitis,idiopathic or simple constipation, diverticular disease, and AIDSenteropathy. Pathophysiology of these disorders eludes logicalexplanation in spite of decades of research and millions of dollars ofresearch funds. A common underlying factor shared by all these disordersobserved by the present inventor is their onset following someextraneous invading infection. In all the disorders, the infectioncannot be demonstrated due to our inability to detect infecting agentswhose cultural characteristics are unknown to medical science.

Circumstantial evidence which suggests that these disorders are“infection-related” includes:

(a) onset following a gastro-intestinal infection which failed tocompletely resolve;

(b) transient improvement with use of certain antibiotics, butrecurrence upon cessation of antibiotics;

(c) transient improvement following orthostatic lavage prior tocolonoscopy and;

(d) transient symptom improvement with use of “colonic” irrigation

It is impractical to use long-term antibiotic therapy (with itsassociated complications) in such patients since cure is not obtainedwith its use. Furthermore, chronic gut infections with recognised,specific pathogens such as Clostridium difficile, Yersiniaenterocolitica or Campylobacter jejuni/coli are not eradicated withantibiotics. Some previous attempts have been made to alter the entericmicroflora in order to eradicate such chronic infections. These measuresnevertheless indicate that alteration of bacterial flora may effectdramatic clinical improvement in conditions characterized by chronic,resistant enterocolitic infection. However there remain many chronicdisorders of uncertain aetiology or causation, which are resistant tocure by current therapeutic techniques.

OBJECTS OF THE INVENTION

It is thus an object of the present invention to provide novel methodsof treating various disease states related to the presence of “abnormal”microflora in the gastrointestinal tract.

DISCLOSURE OF THE INVENTION

The present invention recognises chronic infection/infestation as theunderlying pathological process in a wide range of chronic disorderssuch as irritable bowel syndrome, particularly when characterised bychronic abdominal pain, bloating, or excessive flatulence, together withchronic diarrhoea or alternating constipation/diarrhoea, and also inspastic colon, mucous colitis, collagenous colitis, ulcerative colitis,Crohn's colitis, microscopic colitis, idiopathic inflammatory boweldisease, antibiotic-associated colitis, idiopathic or simpleconstipation, diverticular disease and AIDS enteropathy.

The invention has also been found to relate to other gastrointestinaldisorders of unexplained aetiology such as polyposis coli and colonicpolyps, which may well be influenced by the local bowel microflora.

In addition the present invention also provides a method of treatment ofchronic gastrointestinal infections with specific microorganisms such asClostridium difficile, Yersinia spp, Campylobacter spp, Aeromonas spp,E. coli, Cryptosporidium spp, Amoebae, Giardia and even chronic viralinfections, and of small bowel bacterial overgrowth.

The present invention furthermore, recognises the close associationbetween the intestine and liver disease, and the intestine and migrainesand chronic fatigue syndrome, and possibly other neurological syndromessuch as, multiple sclerosis, amyotrophic lateral sclerosis, myastheniagravis, Parkinson's disease, Alzheimers disease and other degenerativedisorders. Hence, it is proposed that a considerable proportion ofcurrently unexplained diseases of the liver and nervous system ofunknown aetiology may be explicable by the chronic storage of pathogenswithin the small/large intestine and the subsequent passage of antigenicmaterial and pathogenic TOXINS into the portal system (liver damage) orsystemic circulation (neurological conditions). Specifically, suchhepato/biliary system disorders as primary biliary cirrhosis, primarysclerosing cholangitis, fatty liver of unknown aetiology, or cryptogeniccirrhosis, may be secondary to chronic pathogen carrier state in theintestine.

The links between the intestine and joint disease are also recognised.Joint diseases such as rheumatoid arthritis, the non-rheumatoidarthritidies including, ankylosing spondylitis, and Reiter's syndrome,may also be causally related to a chronic intestinal carrier state, asmay other syndromes with an immune mediated component such asglomerulonephritis, haemolytic uraemic syndrome, juvenile diabetesmellitus, Behcet's syndrome, coeliac disease and dermatitisherpetiformis. Similarly, syndromes with an immune complex mediatedcomponent, such as scleroderma, systemic lupus erythematosus, mixedcryoglobulinaemia, polyarteritis, familial Mediterranean fever,amyloidosis, and the various presentations of such syndromes, togetherwith such “idiopathic” states as chronic urticaria, may bemanifestations of variations of immune regulated responses to relatedbowel-origin pathogens chronically shedding their antigen(s) into thecirculation. Other chronic conditions such as acne, and chronicidiopathic pseudo-obstructive syndrome, may well be influenced bysimilar mechanisms.

For many of these syndromes present therapy offers only palliation ofsymptoms and/or the induction of remission of the disease process butnot cure. The present inventor therefore recognised the need to find acurative therapy for these wide ranging disease processes associatedwith considerable morbidity.

Thus according to a first embodiment of the invention there is provideda method of treatment or prophylaxis of a chronic disorder associatedwith the presence in the gastrointestinal tract of a host of abnormal oran abnormal distribution of microflora for said host, which methodcomprises the removal of at least a portion of the host's existingenteric microflora and the substitution of an effective amount ofpredetermined microflora.

In its preferred form the treatment should effect a cure of the symptomsof such disorders. The change of flora is preferably as “near-complete”as possible and the flora is replaced by viable organisms which willcrowd out any remaining, original flora.

The method of the present invention is applicable to animals in generalin particular humans and economically significant domestic animals.

In the case of humans, the present invention encompasses methods oftreatment of chronic disorders associated with the presence of abnormalenteric microflora. Such disorders include but are not limited to thoseconditions in the following categories:

i) gastro-intestinal disorders including irritable bowel syndrome orspastic colon, ulcerative colitis, mucous colitis, collagenous colitis,Crohn's disease, inflammatory bowel disease, microscopic colitis,antibiotic associated colitis, idiopathic or simple constipation,diverticular disease, AIDS enteropathy, small bowel bacterialovergrowth, coeliac disease, polyposis coli, colonic polyps, chronicidiopathic pseudo obstructive syndrome;

ii) chronic gut infections with specific pathogens including bacteria,viruses, fungi and protozoa;

iii) liver disorders such as primary biliary cirrhosis, primarysclerosing cholangitis, fatty liver or cryptogenic cirrhosis;

iv) joint disorders such as rheumatoid arthritis, non-rheumatoidarthritidies, ankylosing spondylitis, and Reiter's syndrome;

v) immune mediated disorders such as glomerulonephritis, haemolyticuraemic syndrome, juvenile diabetes mellitus, mixed cryoglobulinaemia,polyarteritis, familial Mediterranean fever, amyloidosis, scleroderma,systemic lupus erythematosus, and Behcet's syndrome;

vi) neurological syndromes such as migraine, multiple sclerosis,amyotrophic lateral sclerosis, myasthenia gravis, chronic fatiguesyndrome, Parkinson's disease, Alzheimers disease and other degenerativedisorders;

vii) dermatological conditions such as, chronic urticaria, acne,dermatitis herpetiformis and vasculitic disorders;

The above disorders are all characterised by their response to treatmentwith the method of the present invention.

Typically the change in enteric flora comprises:

(a) substantially complete removal of existing enteric flora, and

(b) introduction of an array of predetermined flora into thegastro-intestinal system, and thus in a preferred form the method oftreatment comprises substantially completely changing enteric flora inpatients requiring such treatment.

Furthermore, in some of these disorders a short course of antibioticsmay be required to rid tissue-invasive pathogens originating in thebowel lumen. For example, in Crohn's disease, anti-tuberculosis therapymay be required for six to twelve weeks before the bowel is cleared outand the flora content exchanged for a predetermined flora.

Preferably the removal of existing enteric flora is effected a lavage ofthe gastro-intestinal tract. This can be effected by methods known tothose skilled in the art such as ingestion of lavage solutions such asorthostatic salt and polyethylene glycol solution, enemas or small bowelintubation and lavage.

Turning to the introduction of an array of predetermined flora into thegastro-intestinal system, this can be effected by enemas orper-colonoscope, via intubation of the small bowel using for example alarge bore catheter equipped with distal balloon to effect rapid passagedown the jejunum, or via the oral route with enteric-coated capsules.

The predetermined array of normal bowel microflora preferably comprisesa composition of fresh homologous faeces, equivalent freeze-dried andreconstituted faeces or a “synthetic” faecal composition.

In a preferred form the synthetic faecal composition comprises apreparation of viable flora which preferably in proportional content,resembles normal healthy human faecal flora. Suitable microorganisms maybe selected from the following; Bacteroides, Bifidobacterium,Eubacteria, Fusobacteria, Propionibacteria, Lactobacilli, anaerobiccocci Ruminococcus, E. coli, Gemmiger, Clostridium, Desulfomonas,species and, more specifically, bacteria selected from Table 1.Preferably fungi are also present such as Monilia.

According to a second embodiment of the invention there is provided apharmaceutical composition useful for the treatment and/or prophylaxisof chronic disorders associated with the presence in thegastro-intestinal tract of a host of abnormal or an abnormaldistribution of microflora for said host, which composition comprises aselection of viable microorganisms in appropriate proportions such thatthe composition substantially resembles the host's normal healthy,faecal flora.

In practice suitable microorganisms include those selected fromBacteroides, Bifidobacterium, Eubacteria, Fusobacteria,Propionibacteria, Lactobacilli, anaerobic cocci, Ruminococcus, E. coli,Gemmiger, Clostridium, Desulfomonas, and Monilia species, and morespecifical from those set out in Table 1.

In a preferred form the composition comprises a liquid culture ofBacteroides and E. coli.

The pharmaceutical composition of the present invention is preferablylyophilised, pulverised and powdered. It may then be infused, dissolvedsuch as in saline, as an enema. Alternatively the powder may beencapsulated as enteric-coated capsules for oral administration. As apowder it can preferably be provided in a palatable form forreconstitution for drinking. The composition can be combined with otheradjuvants such as antacids to dampen bacterial inactivation in thestomach. Acid secretion in the stomach could also be pharmacologicallysuppressed using H2-antagonists or omeprazole. The powder may bereconstituted also to be infused via naso-duodenal infusion.

The present composition is therefore preferably in the form of:

i) an enema composition which can be reconstituted with an appropriatediluent;

ii) enteric-coated capsules, or

iii) powder for reconstitution with an appropriate diluent fornaso-enteric infusion or colonoscopic infusion, or

iv) powder for reconstitution with appropriate diluent, flavouring andgastric acid suppression agent for oral ingestion.

Furthermore the present invention also relates to the treatment ofanimals, in particular to the treatment of gastro-intestinal disordersin eccomically important domestic animals, such as cattle, sheep,horses, pigs, goats etc. The method of the present invention has beenfound to be especially useful in the treatment of the various forms ofnecrotising enterocolitis which can be a major problem in animal stocks.

Obviously in the treatment of animals the appropriate composition ofmicroflora will vary according to the species being treated and theconstituent normal flora known to inhabit the gut. Thus the compositionaccording to the invention would comprise, a preparation of viable florawhich preferably in proportional content, resembles the normal healthyfaecal flora of the species involved. The compositions may be preparedin any of the forms already described and administered accordingly.

BEST METHOD OF PERFORMING THE INVENTION

Typically the method of the invention is applicable to a patientsuffering from a chronic disorder associated with the presence ofabnormal microflora in the gastro-intestinal tract such as irritablebowel syndrome.

In the practice of the invention the patients existing enteric flora isremoved by gastro-intestinal lavage effected by ingestion of about 3liters of a balanced salt solution with polyethylene glycol. Lavage iscontinued until the removal of the existing flora is as near complete aspossible.

A composition of predetermined flora in the form of a liquid culture ofBacteroides and E. coli is then infused into the patient per colonoscopein an amount sufficient to replace the removed flora, and reverse thedisease process. Alternatively fresh homologous faeces obtained from adisease screened donor are liquefied and mixed with unprocessed bran.The mixture is then homogenised anaerobically under CO₂ cover andinfused into the patient per colonoscope.

Cure or remission of symptoms is then monitored subjectively and byassessment of stool frequency or other appropriate criteria.

Using liquid cultures of Bacteroides and E. coli the inventor hasachieved total reversal of colitis, irritable bowel syndrome andconstipation.

As indicated in the method of treatment aspect of the invention, apreparatory course of appropriate antibiotics may be used. For example.Septrin for chronic yersiniasis, Metronidazole for ulcerative colitis,anti-TB therapy in Crohn's disease, or Vancomycin in chronic Clostridiumdifficile infestations.

TABLE 1 % of flora^(b) Organism(s) 11.8(0.90) Bacteroides fragilis ss.vulgatus  9.9(0.83) Eubacterium aerofaciens  8.9(0.78) Bacteroidesfragilis ss. thetaiotaomicron  6.6(0.68) Peptostreptococcus productus II 6.0(0.64) Bacteroides fragillis ss. distasonis  4.4(0.55) Fusobacteriumprausnitzii  3.5(0.49) Coprococcus eutactus  3.0(0.45) Eubacteriumaerofaciens III  2.8(0.44) Peptostreptococcus productus I  2.7(0.43)Ruminococcus bromii  2.6(0.43) Bifidobacterium adolescentis  2.2(0.39)Gemmiger formicilis, Bifidobacterium longum  2.1(0.38) Eubacteriumsiraeum  1.8(0.35) Ruminococcus torques  1.7(0.34) Eubacterium rectaleIII-H  1.6(0.33) Eubacterium rectale IV, Eubacterium eligens  1.5(0.32)Bacteroides eggerthii  1.4(0.31) Clostridium leptum  1.3(0.29)Bacteroides fragilis ss. a  1.2(0.29) Eubacterium biforme  0.91(0.25)Bifidobacterium infantis  0.84(0.24) Eubacterium rectale III-F 0.57(0.20) Coprococcus comes, Bacteroides capillosus  0.50(0.18)Ruminococcus albus, Eubacterium formicigenerans, Eubacterium hallii,Eubacterium ventriosum I, Fusobacterium russii  0.43(0.17) Ruminococcusobeum, Eubacterium rectale II, Clostridium ramosum I, Lactobacillusleichmanii  0.35(0.16) Ruminococcus callidus, Butyrvibrio crossotus 0.30(0.14) Acidaminococcus fermentans, Eubacterium ventriosum,Bacteroides fragilis ss. fragilis, Bacteroides AR  0.23(0.12)Coprococcus catus, Eubacterium hadrum, E. cylindroides, E. ruminantium,Eubacterium CH-1 , Staphylococcus epidermidis  0.17(0.10)Peptostreptococcus BL, Eubacterium limosum, Bacteroides praeacutus,Bacteroides L, Fusobacterium mortiferum I, F. naviforme, Clostridiuminnocuum, C. ramosum, Propionibacterium acnes, Ruminococcus flavefaciens 0.10(0.08) Ruminococcus AT, Peptococcus AU-1, Eubacterium AG, -AK, -AL,-AL-1, -AN; Bacteroides fragilis ss. ovatus, -ss. d, -ss. f; BacteroidesL-1, L-5; Fusobacterium nucleatum, F. mortiferum, Esherichia coli,Streptococcus morbillorum  0.05(0.05) Peptococcus magnus, Peptococcus G,-AU-2; Streptococcus intermedius, Ruminococcus lactaris, RuminococcusCO, Gemmiger X, Coprococcus BH, -CC; Eubacterium tenue, Eubacteriumramulus, Eubacterium AE, -AG-H, -AG-M, -AJ, -BW-1; Bacteroidesclostridiiformis ss. clostridiiformis, B. coagulans, B. oralis, B.ruminicola ss. brevis, -ss. ruminicola, Bacteroides splanchnicus,Desulfomonas pigra, Bacteroides L-4, -W-1; Fusobacterium H,Lactobacillus G, Succinivibrio A ^(b)The percentage of the fecalpopulation (the standard deviation of the estimate is given inparentheses).

The invention will now be further described with reference to thefollowing non-limiting examples.

EXAMPLE 1

A 28 year old male presented with bloody diarrhoea, 7 to 12 times perday, weight loss, anaemia, arthritis, marked liver-function blood testabnormalities, colonoscopic findings of “pancolitis” and histologicdiagnosis of active chronic colitis. Following two years of “standard”anti-colitis therapy he improved markedly. The anaemia was corrected, hegained weight and his liver functions improved somewhat. However, hecontinued to experience three to four stools per day in spite of 9×500mg salazopyrin tablets per day and second-nightly steriod enemas(Predsol Enemas). Furthermore, liver function tests remained elevated.Following one week of metronidazole tablets 200 mg×4 per day, and oralingestion of three liters balanced salt solution with polyethyleneglycol (GLYCOPREP), he received fresh, liquefied homogenized human donorfaeces from a disease-screened donor were infused into the patient.Prior to infusion unprocessed bran was added to the faeces andhomogenization was carried out anaerobically under CO₂ cover.

Following infusion, the patient has remained well and off all treatmentfor three months to date. Liver function tests have returned to normal.He has one formed stool per day and has begun to put on weight. He hasno arthralgia.

EXAMPLE 2

Similar methods were used to treat 55 patients suffering with eitherconstipation, diarrhoea, abdominal pain, ulcerative colitis or Crohn'sdisease. Patients were treated when other forms of therapy had failed tocontrol their symptoms. Following bowel flora alteration 20 patientswere deemed “cured”, 9 improved, while 26 failed to improve. Thefollowing cases illustrate “cures” using the method of the inventionover a follow up period of 1 to 12 months.

Case 1 Chronic Constipation

A 31 year old female who had a history of chronic constipationcommencing at birth with a frequency of once per week without laxatives.Following bowel flora alteration she has had daily or second stoolfrequency, without resort to laxatives and remains well at six monthfollow-up.

Case 2 Chronic Pain-Predominant IES

This 21 year old female was thoroughly investigated over a four yearperiod for severe colickly abdominal pain, requiring frequent admissionsand narcotic pain relief. Multiple investigations included endoscopy,laparoscopy and laparotomy. Five days following alteration of her bowelflora she was pain free and remains pain free at four months follow-up.

Case 3 Chronic Diarrhoea-Predominant IBS

A 35 year old female presented with a history of several years ofdiarrhoea (2-10/d) and associated abdominal pain. Her only abnormalinvestigation was +ve stool latex test for clostridium difficile toxin.This failed to clear after a course of Vancomycin and she underwentbowel flora alteration with resolution of her chronic diarrhoea.Diarrhoea and pain have not recurred at one month follow-up.

Case 4 Chronic Ulcerative Colitis

This 45 year old man presented with an 18 month history of ulcerativecolitis and elevated liver transaminases. Pancolitis was confirmed oncolonoscopy. Sulfasalazine caused a rash while olsalazine gaveinadequate relief. The patient underwent exchange of bowel floraimproving adequately enough to come off treatment within days. At threemonths he continues to feel well, has no diarrhoea and is on nomedication. His liver transaminases have returned to normal. Colonoscopyis now normal and mucosal biopsies are now normal.

Case 5 Crohn's Disease

This 31 year old man was admitted to hospital with small bowelobstruction subsequently shown on small bowel enema to be Crohn'sdisease of the terminal ileum. This was confirmed on terminal ilealbiopsy. In spite of prednisone and sulfasalazine, hypoproteinaemia withankle oedema was prominent presumably due to protein losing enteropathy.Three days following bowel flora alteration his ankle oedema and serumproteins returned to normal. He remains free of symptoms, off therapy 4months later.

Case 6 Irritable Bowel/chronic Fatigue Syndrome

This 42 year old woman presented with symptoms of irritable bowelsyndrome characterised by diarrhoea and pain, and also complained ofprofound tiredness. Faecal infusion reversed the bowel symptoms. Inaddition the profound tiredness suddenly disappeared. Similar resultswere obtained in 4 related cases.

What is claimed is:
 1. A method for the treatment of a chronicgastro-intestinal disorder selected from the group consisting of spasticcolon, mucous colitis, collagenous colitis, inflammatory bowel disease,microscopic colitis, idiopathic or simple constipation, diverticulardisease, chronic idiopathic pseudo obstructive syndrome and chronicenteric infections, in an adult human host, where the causative agent isunknown, which method comprises substantially completely removing thehost's existing enteric microflora by a method comprising using alavage, and the substitution of an effective amount of fresh or dried orreconstituted feces from a disease-screened human donor or theadministration of an effective amount of a pharmaceutically acceptablecomposition comprising microorganism selected from the group consistingof Batcteroides and E. coli in liquid culture or dried viable form. 2.The method of claim 1 wherein said composition comprises Bacteroides. 3.The method of claim 1 wherein said composition comprises E. coli.
 4. Themethod of claim 1 wherein the composition further comprises at least onemicroorganism selected from the group consisting of: Bifidobacterium,Eubacteria, Fusobacteria, Propionibacteria, Lactobacilli, anaerobiccocci, Ruminococcus, Gemmiger, Clostridium, Desulfomonas, Moniliaspecies, and mixtures thereof.
 5. The method of claim 1 wherein theremoval of existing enteric microflora is carried out bygastro-intestinal lavage with orthostatic salt solution and polyethyleneglycol solution.
 6. The method of claim 5 wherein gastro-intestinallavage is effected by enemata, oral ingestion or per enteral infusion.7. The method of claim 1 wherein the composition is introduced into thepatient's gastro-intestinal system by ingestion or by per enteralinfusion.
 8. The method of claim 1 further comprising the administrationof an effective amount of at least one antibiotic prior to the removalof the existing enteric microflora.
 9. A method for the treatment of achronic gastro-intestinal disorder selected from the group consisting ofulcerative colitis, Crohn's disease, and irritable bowel syndrome, in anadult human host, where the causative agent is unknown, which methodcomprises substantially completely removing the host's existing entericmicroflora by a method comprising using a lavage, and the substitutionof an effective amount of fresh or dried or reconstituted feces from adisease-screened human donor or the administration of an effectiveamount of a pharmaceutically acceptable composition comprisingmicroorganism selected from the group consisting of Bacteroides and E.coli in liquid culture or dried viable form.
 10. The method of claim 9wherein said composition comprises, Bacteroides.
 11. The method of claim9 wherein said composition comprises E. coli.
 12. The method of claim 9wherein the composition further comprises at least one microorganismselected from the group consisting of: Bifidobacterium, Eubacteria,Fusobacteria, Propionibacteria, Lactobacilli, anaerobic cocci,Ruminococcus, Gemmiger, Clostridium, Desulfomonas, Monilia species, andmixtures thereof.
 13. The method of claim 9 wherein the removal ofexisting enteric microflora is carried out by gastro-intestinal lavagewith orthostatic salt solution and polyethylene glycol solution.
 14. Themethod of claim 13 wherein gastro-intestinal lavage is effected byenemata, oral ingestion or per enteral infusion.
 15. The method of claim9 wherein the composition is introduced into the patient'sgastro-intestinal system by ingestion or by per enteral infusion. 16.The method of claim 9 further comprising the administration of aneffective amount of at least one antibiotic prior to the removal of theexisting enteric microflora.
 17. The method of claim 8 wherein saidantibiotic is metronidazole.
 18. The method of claim 16 wherein saidantibiotic is metronidazole.
 19. A method for treating a chronicdisorder associated with the presence of abnormal enteric microflora inan individual comprising substantially completely removing the existingenteric microflora of the individual by a lavage and the administrationin place thereof of an effective amount of fresh or dried orreconstituted feces from a disease screened donor or of apharmaceutically acceptable composition comprising microorganismselected from the group consisting of Bacteroides and E. coli in liquidculture or dried viable form.
 20. The method of claim 19 where thelavage is performed with orthostatic salt solution and polyethyleneglycol solution.
 21. The method of claim 19 where the lavage is effectedby enema, oral ingestion or per enteral infusion.
 22. The method ofclaim 19 further comprising the administration of an effective amount ofat least one antibiotic prior to the removal of the existing microflora.23. The method of claim 22 wherein said antibiotic is metronidazole. 24.The method of claim 19 wherein the administration is of apharmaceutically acceptable composition comprising Bacteroides and E.coli.
 25. The method of claim 24 where the composition further comprisesClostridium.
 26. The method of claim 19 wherein the composition furthercomprises at least one microorganism selected from the group consistingof Bifidobacterium, Eubacteria, Fusobacteria, Propionibacteria,Lactobacilli, anaerobic cocci, Ruminococcus, Gemmiger, Clostridium,Desulfomonas, Monilia species, and mixtures thereof.
 27. The method ofclaim 19 where the chronic disorder is a chronic gastro-intestinaldisorder.
 28. A method for treating a chronic gastro-intestinal disorderin an individual comprising substantially completely removing theexisting enteric microflora of the individual by a lavage and theadministration in place thereof of an effective amount of fresh or driedor reconstituted feces from a disease screened donor or of apharmaceutically acceptable composition comprising microorganismselected from the group consisting of Bacteroides and E. coli in liquidculture or dried viable form.
 29. The method of claim 27 wherein theadministration is of an effective amount of a pharmaceuticallyacceptable composition comprising Bacteroides and E. coli.
 30. Themethod of claim 29 wherein the composition further comprisesClostridium.